Advisor(s)

Vladimir P. Torchilin

Contributor(s)

Roger W. Giese, Kim Lewis, Robert A. Schatz, M. V. Sitkovskiĭ.

Date of Award

1-2012

Date Accepted

1-2012

Degree Grantor

Northeastern University

Degree Level

Ph.D.

Degree Name

Doctor of Philosophy

Department or Academic Unit

Bouve College of Health Sciences. Department of Pharmaceutical Sciences

Keywords

Cancer Biomarkers, Detection, Imaging, Micelles, Quantum Dots, Theranostics

Disciplines

Pharmacy and Pharmaceutical Sciences

Abstract

Nanopreparations, such as micelles, liposomes and polymeric microcapsules are used to incorporate diagnostic and therapeutic agents in order to improve their performance. Lipid-core nanopreparations composed of polymeric micelles were employed to incorporate quantum dots for near infrared imaging of tumors. Tumors were imaged rapidly at half the dose of a commercially available quantum dot formulation. Additionally, these quantum dots containing polymeric micelles were targeted with a cancer-specific monoclonal antibody (2C5) that selectively accumulated in the tumor. This system produced a higher signal compared to untargeted quantum dot micelles.

Cancer was also detected indirectly by making use of circulating biomarkers, such as nucleosome and carcinoembryogenic antigen. A microchip-based diagnostic tool was fabricated that detected low levels of these biomarkers. The device was sensitive enough to capture picogram concentrations of antigens in biological fluids. Tumor development could be tracked by following the cancer biomarker levels. This system proved to be more sensitive than commercially available ELISA kit. Thus, it may aid in the detection of small changes in biomarker levels associated with an early cancer stage.

In a combined diagnostic and therapeutic approach, a micellar nanoparticle that incorporated both superparamagnetic iron oxide nanoparticles and paclitaxel for application as a theranostic agent was developed and characterized in vitro and in vivo.

Document Type

Dissertation

Rights Holder

Jaydev Rajaram Upponi


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